Distinct oral-associated gastric microbiota and communities for spatial microbial heterogeneity in gastric cancer.

Unlabelled: The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors ( for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including -positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of and oral-associated bacteria was verified using fluorescence hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included , , and , was more abundant in the upper third of the GC. However, was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with in the lower third site of the GC tumoral tissue. Importantly, -negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in -positive GC patients showed no difference in overall survival. The prevalence of in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species and were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for -negative GCs.

Importance: Our study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species and were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for -negative GCs.